EP0819027B1 - Wanderfeldscheider zur trennung von partikeln - Google Patents

Wanderfeldscheider zur trennung von partikeln Download PDF

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Publication number
EP0819027B1
EP0819027B1 EP96909267A EP96909267A EP0819027B1 EP 0819027 B1 EP0819027 B1 EP 0819027B1 EP 96909267 A EP96909267 A EP 96909267A EP 96909267 A EP96909267 A EP 96909267A EP 0819027 B1 EP0819027 B1 EP 0819027B1
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EP
European Patent Office
Prior art keywords
electrodes
particles
particle
electrode
travelling wave
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
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EP96909267A
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English (en)
French (fr)
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EP0819027A1 (de
Inventor
Andrew Nicholas Dames
Nicholas Archibald Safford
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Scientific Generics Ltd
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Scientific Generics Ltd
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Publication date
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Publication of EP0819027A1 publication Critical patent/EP0819027A1/de
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02—Separators
    • B03C5/022—Non-uniform field separators
    • B03C5/028—Non-uniform field separators using travelling electric fields, i.e. travelling wave dielectrophoresis [TWD]

Definitions

  • travelling wave particle separation apparatus which may be travelling wave field migration (also known as travelling wave dielectrophoresis) apparatus, having an improved electrode configuration.
  • travelling wave field migration also known as travelling wave dielectrophoresis
  • particles can be manipulated by subjecting them to travelling electric fields.
  • travelling fields are produced by applying appropriate voltages to microelectrode arrays of suitable design.
  • the microelectrodes have the geometrical form of parallel bars, which may be interrupted by spaces to form channels, as shown in figure 1 and may be fabricated using standard metal sputtering and photolithographic techniques as described by Price, Bury and Pethig, Biochemica et Biophysica, Vol.964, pp.221-230.
  • Travelling electric fields are generated by applying voltages of suitable frequency and phases to the electrodes as described in a paper, title "Separation of small particles suspended in liquid by nonuniform travelling field", by Masuda, Washizu and Iwadare, IEEE Transactions on Industry Applications, Vol.IA-23, pp.474-480.
  • Masuda and his coworkers describe how a series of parallel electrodes (with no channels) supporting a travelling electric field can, in principle, be used to separate particles according to their electrical charge and size (weight).
  • Masuda et al have not however described a practical demonstration of such a particle separation method.
  • travelling wave dielectrophoresis this is something of a misnomer as the force which acts on the particles to produce translational movement is not the dielectrophoresis force but rather that which acts in electrorotation.
  • This force is related to the imaginary component of the polarisability of the particle within its surrounding medium.
  • particle migration only occurs for travelling wave frequencies which produce negative dielectrophoretic forces on the particle. (Dielectrophoretic forces are related to the real component of the polarisability of the particle within its surrounding medium.) These forces are responsible for lifting the particle away from the electrodes and the channel between the electrodes.
  • TWFM traveling wave field migration
  • the frequency selected has to be such that the imaginary component of the dipole moment induced in the particles is non-zero (whether positive or negative) to produce a force displacing the particles along the array of electrodes.
  • the field conditions may also be chosen such that some particles are held by the electrodes and do not migrate or follow any bulk flow of the liquid in which they are contained whilst other particles are not held by the electrodes and are either essentially unaffected or migrate in one or other direction with respect to the field.
  • an array of electrodes is provided forming a "ladder" along which particles may be caused to migrate under suitable field conditions or on which particles may be held.
  • the electrodes may form a linear ladder or may be arranged as concentric circles.
  • the phase of the voltage applied to successive electrodes will differ in a repeating pattern so that each n th electrode will be at the same phase (where n is an integer).
  • travelling wave particle separation apparatus having an electrode array which comprises a plurality of continuous electrodes running side by side with one another in a path so shaped that a particle migrating transverse to the electrodes would cross each electrode repeatedly and such that the order in which the electrodes would be encountered by such a particle migrating transverse to the electrodes at each crossing thereof would be the same, wherein the electrode array comprises a helical spiral of constant or decreasing diameter from one end of the helix to the other.
  • the particles are not necessarily actually caused to migrate over the electrode array in the use of the apparatus.
  • the electrode arrangements in accordance with the invention are a helix of constant diameter, or a helix of decreasing diameter, i.e. a conical spiral.
  • the nature of the particles which are separated may vary widely.
  • the particle may be of a size to be visible using a light microscope (a microscopic particle) or may be smaller (a sub-microscopic particle).
  • the particle may be labelled to assist identifying or tracing it and may be detected using labels such as luminescent, fluorescent and electromagnetic radiation absorbent labels.
  • Examples of the former type of particle include mammalian cells, plant cells, yeast cells, plastics microbeads, chromosomes undergoing meiosis and mitosis and oocytes.
  • Examples of the second type would include bacterial cells, viruses, DNA or RNA molecules, proteins, other bio-molecules, and chromosomes.
  • Methods of altering field migration properties are described in detail in W094/16821.
  • Electrodes There are preferably from 2 to 10 electrodes, more preferably from 2 to 5 electrodes. As the electrodes are continuous, there is only a need to make one electrical connection per electrode for the whole apparatus and so the need for numerous or crossing connection paths is avoided.
  • the process of travelling wave particle separation may be carried out using an array of electrodes subjected to phased electric fields normally such that every n th (where n is an integer) electrode is in phase.
  • This periodicity defines the effective wave length of the travelling wave field produced.
  • This wave length is optimally about ten times the average diameter of the particle to be moved under TWFM, eg from 5 to 20 times or more preferably 8 to 12 times said average diameter. For particles which are not roughly circular, it is the length in the direction transverse to TWFM movement which is of significance
  • the electrodes may be formed, depending on the dimensions required, using any of the standard techniques for patterning and manufacturing microscopic structures.
  • the electrodes can be produced by:
  • Figure 1 shows an arrangement of electrodes for use in the invention.
  • Electrodes 1, 2, 3, 4 there are four electrodes 1, 2, 3, 4 to which are applied sinusoidal voltages of phases 90° apart, as shown. If the apparatus is run so as to cause migration of particles, the particles will migrate, crossing the electrodes repeatedly, but always in the order 1, 2, 3 and 4.
  • a sample may be applied to the whole area of the electrode and the frequency of the field may be chosen such that particles to be separated are attracted to the electrodes and are thus immobilised by the electrodes whilst other particles are repelled by the electrodes and so remain free.
  • the free particles may be washed away.
  • the field conditions may be selected such that certain particles migrate toward the centre and others migrate toward the ends, so that the particles are separated and may be collected.
  • Electrodes are formed on the outer or more inner surface of a cylindrical former about which they follow a helical path. Once again, only four wiring connections are needed.
  • a liquid may be flowed over the electrode array axially of the helix and particles attracted to the electrodes may be harvested later by turning off the field and washing.
  • the electrode array may be used as a field migration path for separating particles.
  • the sample volume will be limited essentially by the area of the electrode array. As compared with the electrode arrays described in WO 94/16821, the electrode arrays shown here may be constructed to handle a much larger volume. Thus whilst the earlier electrode arrays were adapted to deal with a sample volume of about 10 ⁇ l, the electrode arrays described above may be sized to accept samples of greater than 5 ml, eg up to 50 ml or more.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Electrostatic Separation (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)
  • Surface Acoustic Wave Elements And Circuit Networks Thereof (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Claims (2)

  1. Wanderfeld-Teilchenseparationsapparat mit einer Elektrodenanordnung, die eine Mehrzahl von fortlaufenden Elektroden (1, 2, 3, 4) aufweist, die Seite an Seite auf einer Bahn verlaufen, die so geformt ist, dass ein quer zu den Elektroden wanderndes Teilchen jede Elektrode wiederholt kreuzen würde und dass die Reihenfolge, in der ein solches quer zu den Elektroden wanderndes Teilchen den Elektroden begegnen würde, bei jedem Kreuzen die gleiche wäre, dadurch gekennzeichnet, dass die Elektrodenanordnung eine schraubenförmige Spirale von Seite an Seite liegenden Elektroden aufweist, wobei die Anordnung einen konstanten Durchmesser oder einen von einem Ende der Schraube zum anderen abnehmenden Durchmesser hat.
  2. Apparat nach Anspruch 1, wobei zwei bis zehn Elektroden in der Mehrzahl vorhanden sind.
EP96909267A 1995-04-06 1996-04-04 Wanderfeldscheider zur trennung von partikeln Expired - Lifetime EP0819027B1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9507125.4A GB9507125D0 (en) 1995-04-06 1995-04-06 Travelling wave electrodes
GB9507125 1995-04-06
PCT/GB1996/000860 WO1996031282A1 (en) 1995-04-06 1996-04-04 Travelling wave particle separation apparatus

Publications (2)

Publication Number Publication Date
EP0819027A1 EP0819027A1 (de) 1998-01-21
EP0819027B1 true EP0819027B1 (de) 2000-06-21

Family

ID=10772628

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96909267A Expired - Lifetime EP0819027B1 (de) 1995-04-06 1996-04-04 Wanderfeldscheider zur trennung von partikeln

Country Status (7)

Country Link
US (1) US6059950A (de)
EP (1) EP0819027B1 (de)
JP (1) JPH11503072A (de)
AT (1) ATE193981T1 (de)
DE (1) DE69608958T2 (de)
GB (1) GB9507125D0 (de)
WO (1) WO1996031282A1 (de)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5993630A (en) * 1996-01-31 1999-11-30 Board Of Regents The University Of Texas System Method and apparatus for fractionation using conventional dielectrophoresis and field flow fractionation
US5888370A (en) * 1996-02-23 1999-03-30 Board Of Regents, The University Of Texas System Method and apparatus for fractionation using generalized dielectrophoresis and field flow fractionation
GB9619093D0 (en) 1996-09-12 1996-10-23 Scient Generics Ltd Methods of analysis/separation
US5858192A (en) * 1996-10-18 1999-01-12 Board Of Regents, The University Of Texas System Method and apparatus for manipulation using spiral electrodes
WO2000077163A1 (fr) 1999-06-10 2000-12-21 Matsushita Electric Industrial Co., Ltd. Dispositif electrochimique deplaçant des particules enrobees d'une proteine
AU2001271330A1 (en) 2000-06-14 2001-12-24 Board Of Regents, The University Of Texas System Method and apparatus for combined magnetophoretic and dielectrophoretic manipulation of analyte mixtures
DE60113287D1 (de) 2000-06-14 2005-10-13 Univ Texas Systeme und verfahren zur zellteilbevölkerungsanalyse
US7004238B2 (en) * 2001-12-18 2006-02-28 Illinois Institute Of Technology Electrode design for electrohydrodynamic induction pumping thermal energy transfer system
US20040011652A1 (en) * 2002-07-16 2004-01-22 Bressler Vincent Edward Separation of particles using multiple conductive layers
US7384791B2 (en) * 2004-01-21 2008-06-10 Hewlett-Packard Development Company, L.P. Method of analyzing blood
US7160425B2 (en) * 2004-03-25 2007-01-09 Hewlett-Packard Development Company, L.P. Cell transporter for a biodevice
US7390388B2 (en) * 2004-03-25 2008-06-24 Hewlett-Packard Development Company, L.P. Method of sorting cells on a biodevice
US7390387B2 (en) * 2004-03-25 2008-06-24 Hewlett-Packard Development Company, L.P. Method of sorting cells in series
GB0812996D0 (en) * 2008-07-16 2008-08-20 Blood Analysis Ltd Electrode arrangement for analysing concentrations of particles

Family Cites Families (17)

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Publication number Priority date Publication date Assignee Title
GB423523A (en) * 1933-08-04 1935-02-04 Bernard Whelpton Holman Improvements in apparatus for the electro-magnetic separation or concentration of minerals
US3294237A (en) * 1963-05-31 1966-12-27 Weston David Magnetic separator
US3778678A (en) * 1972-02-16 1973-12-11 S Masuda Apparatus for electric field curtain of contact type
JPS5948144B2 (ja) * 1976-02-28 1984-11-24 株式会社井上ジャパックス研究所 固液分離装置
US4390403A (en) * 1981-07-24 1983-06-28 Batchelder J Samuel Method and apparatus for dielectrophoretic manipulation of chemical species
WO1985002762A1 (en) * 1983-12-21 1985-07-04 Kharkovsky Nauchno-Issledovatelsky Institut Obsche Bipolar electrocoagulator
US4988208A (en) * 1987-10-08 1991-01-29 Koshin Kenki Kogyo Co., Ltd. Method of and apparatus for mixing or dispersing particles
US4970154A (en) * 1987-10-09 1990-11-13 Baylor College Of Medicine Method for inserting foreign genes into cells using pulsed radiofrequency
US5108568A (en) * 1989-07-07 1992-04-28 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Controlled method of reducing electrophoretic mobility of macromolecules, particles or cells
US5284558A (en) * 1990-07-27 1994-02-08 University Of Iowa Research Foundation Electrophoresis-based sequencing of oligosaccharides
DE4034697A1 (de) * 1990-10-31 1992-05-14 Fraunhofer Ges Forschung Verfahren zur handhabung mikroskopisch kleiner, dielektrischer teilchen und vorrichtung zur durchfuehrung des verfahrens
EP0519250A3 (en) * 1991-06-10 1993-06-02 Miles Inc. Microparticle-labeled binding assay analyzed by microwave spectroscopy
US5228960A (en) * 1992-07-17 1993-07-20 Beckman Instruments, Inc. Analysis of samples by capillary electrophoretic immunosubtraction
GB9301122D0 (en) * 1993-01-21 1993-03-10 Scient Generics Ltd Method of analysis/separation
US5514150A (en) * 1994-03-03 1996-05-07 Lsi Logic Corporation Micromachined conveyor devices
US5431793A (en) * 1994-07-29 1995-07-11 Beckman Instruments, Inc. Quantitative analysis of glycosylated hemoglobin by immunocappillary electrophoresis
US5858192A (en) * 1996-10-18 1999-01-12 Board Of Regents, The University Of Texas System Method and apparatus for manipulation using spiral electrodes

Also Published As

Publication number Publication date
WO1996031282A1 (en) 1996-10-10
ATE193981T1 (de) 2000-07-15
EP0819027A1 (de) 1998-01-21
JPH11503072A (ja) 1999-03-23
US6059950A (en) 2000-05-09
DE69608958T2 (de) 2000-10-19
GB9507125D0 (en) 1995-05-31
DE69608958D1 (de) 2000-07-27

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